Other changes in the blood are alleged, like lessening of the albumen, as balancing the increase of fibrine, and lipæmia, but the constancy of these in all cases of inflammation is uncertain.

By way of comment and explanation of the above changes in the circulation the following may be advanced: The primary contraction of the capillaries is by no means a necessary condition of inflammation, and contractions and dilatations within certain limits occur in health and as a purely physiological act. The dilatation of the capillaries and the increased flow of blood to the part are related to each other as in part cause and effect, yet both are due to a reflex act from the seat of irritation which inhibits contraction in the capillaries and determines a more rigid contraction in the walls of the arteries running to the part. A rigid inelastic vessel of the same calibre and under the same pressure transmits more liquid than the one with elastic walls. The movement of the white globules to the walls of the vessel depends in part on their levity, light bodies passing into the outer slow moving layer, which is less dense, from the central stream where the force and density are greater. The epithelial cells of the intima undergo cloudy swelling and are often detached, allowing the readier migration of the globules through the openings of the lymphatics and the softened and friable walls. When the capillaries are blocked the pressure necessarily increases on the arterial side, favoring laceration of the friable walls and the escape of minute masses of blood. The formation of the buffy coat is characteristic of the normal equine blood; in inflammation it becomes more abundant. In the other genera a buffy coat apart from inflammation may be shown in: (a) anæmia or oligocythæmia in which the blood is deficient in red globules; (b) in plethora in which there is an excess of blood solids; (c) in pregnancy in which there is an excess of white and small red globules; (d) in violent exertion or over-excitement, in which the blood has circulated with extraordinary rapidity. The all-sufficiency of the tissue cells in determining inflammation may be deduced from the following experiment. A ligature is tied around a frog’s thigh so tightly as to arrest circulation, and the leg amputated above the ligature; mustard is then applied to the web of the foot and a blister rises precisely as though circulation continued.

MICROBES, DIAPEDESIS AND PHAGOCYTOSIS.

The rôle of microbes in inflammation is much greater than was formerly supposed. It is now demonstrated that a large class of inflammations are directly caused by the colonization of microbes in the tissue and by the local irritation caused by their ptomaines and toxins. We must also admit the direct action of the latter on the heat producing and vaso-motor nervous centres, as a factor more or less potent in different cases in the causation and maintenance of inflammation. No less important is the relation of the microbe to the migration of the globules and the subsequent results of the inflammation. This influence microbes share with certain chemical agents. Migration may be greatly checked even in inflamed parts by the hypodermic or intravenous injection of sulphate of quinia, eucalyptol, salicylic acid, or iodoform. Some have thought these acted by a chemiotactic attraction, but quinia is otherwise found to repel the leucocytes. Their action on the leucocytes or capillary walls is problematic.

Chemiotaxis is that power by which a microbe or any element attracts or repels the leucocytes. When it attracts the chemiotaxis is said to be positive, when it repels it is negative. Among negative chemiotactic agents are quinia, solutions of sodium chloride (10%), and potassium salts, lactic acid, alcohol (10%), chloroform, glycerine, jequirity, and bile. To some agents, (creatine, creatinine, allantoin, peptone, phlorydzine,) leucocytes are indifferent. To gluten, wheat casein, pea legumin and the great majority of pathogenic microbes, leucocytes are positively attracted. As microbes exercise a great influence in producing local inflammation, so they are important factors in procuring an abundant emigration of leucocytes. Some of the most fatal of microbian diseases, like fowl cholera, repel leucocytes, and the benefit of their defensive work is to a large extent lost. The toxins of the chemiotactic microbe filtered from the bacteria exert the same influence as the living bacteria, as shown by Gabritchevski, Massart and Bordet.

But chemiotaxis may be exerted from within the bloodvessel as well as from without. Bouchard, Massart and Bordet have shown that a tube containing a culture of bacillus pyocyanus, introduced beneath the skin of a rabbit attracts in a few hours a great number of leucocytes. But if, immediately after its introduction, ten cubic centimetres of a sterilized culture of the same bacillus are injected into a vein, very few leucocytes enter the tube inserted under the skin. The chemiotaxis seems to operate in this case from within the blood, and the desires of the leucocytes are satisfied without leaving the vessel. It would seem that in such cases the migration and protective work of the leucocytes is best exerted at the outset of the illness and before the toxic products have been poured into the blood in any quantity, whereas in the advanced stages when the blood is charged with ptomaines and toxins migration and phagocytosis would be likely to be limited and ineffective. The same consideration would forbid the use of drugs that check migration in all cases of attacks by microbes for which leucocytes have a positive chemiotaxis.

Phagocytosis is the act by which the leucocytes englobe and dissolve the invading microbe. By its amœboid movement the leucocyte flows around, and envelopes the microbe for which it has a positive chemiotaxis, and then begins the struggle of vitality between the two living germs. If the poison (leucomaine antitoxin,) and digestive ferment (enzyme) of the leucocytes are more deadly to the invading germ, than its ptomaines, toxins and enzymes are to the leucocyte, the white cell comes off the victor, and recovery takes place, but if the converse obtains the triumph is on the side of the microbe. As a rule much depends on the more or less deadly nature of the products of the invading microbe, on the numbers of the germ, the rapidity of its proliferation, and the consequent amount of its toxic products thrown into the system, on the one hand: And on the other the potency of the chemiotaxis of the leucocyte for the invading germ, the number of white cells that emigrate into the inflamed tissue and engage in the work of phagocytosis, and on whether the particular animal system and its white cells have sustained a previous attack by the same germ and has thereby been educated to produce a greater amount of the defensive proteids (leucomaine, antitoxin, enzyme) than it naturally would (acquired immunity).

Even with an abundant emigration of the leucocytes into the inflamed or invaded tissue, a number, greater or less, are usually destroyed by the bacterial poisons and pass into degeneration or liquefaction, as in the formation of pus, and yet the attacking germ may be overcome, destroyed and devoured by the rapidly increasing survivors. In general terms the migration of the cells is in inverse ratio to the susceptibility of the animal to the microbe or the disease which it causes.

The positive and negative chemiotaxis, which determine phagocytosis or prevent it, may be seen in the action of the leucocytes toward the germs of two diseases, to one of which the animal is susceptible and to the other of which it is not. Thus the leucocytes of the pigeon take in the bacillus anthracis and suffer nothing apparently, whereas the same white cells of the dove are repelled by the bacteria of fowl cholera which are not therefore found in their interior.

The leucocytes that migrate from the bloodvessels are in the main, the most numerous, (the neutrophile or polynuclear) form; the mononuclear leucocytes with horseshoe shaped nucleus also migrate but in much fewer numbers and are as a rule less occupied in phagocytosis. At the same time, these two forms may show each a preference for a particular microbe, the polynuclear cell sometimes devouring one which the mononuclear cell rejects, and the mononuclear cell taking in one which the polynuclear refuses.